Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.
Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.
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DOI：
10.1523/jneurosci.6451-10.2011
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发表时间：
2011-03-30
期刊：
影响因子：
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通讯作者：
Basbaum AI
中科院分区：
文献类型：
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作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
热和辣椒素受体TRPV1是初级传入疼痛纤维（伤害感受器）检测疼痛热所必需的，但功能性TRPV1通道在中枢神经系统（CNS）中表达的程度存在争议。由于以前的证据主要是基于对辣椒素的间接生理反应，在这里，我们对TrpV1基因座进行了遗传修饰，以优异的灵敏度和特异性揭示了TRPV1在所有神经元和非神经元组织中的分布。与在CNS中广泛和稳健表达的报道相反，我们发现神经元TRPV1在很大程度上限于初级感觉神经节中的伤害感受器，在一些离散的脑区域中表达最少，最显著的是在尾侧下丘脑内和邻近的连续带细胞中。我们确认下丘脑表达的小鼠使用几种互补的方法，包括原位杂交，钙成像，和电生理记录。在大鼠、猴和人脑中的其他原位杂交实验表明，TRPV1在CNS中的限制性表达在物种间是保守的。在中枢神经系统外，我们发现TRPV1在体温调节组织内的小动脉平滑肌细胞亚群中表达。在这里，辣椒素增加钙的摄取并诱导血管收缩，这种作用可能会抵消神经元TRPV1激活产生的血管舒张。
The heat and capsaicin receptor, TRPV1, is required for the detection of painful heat by primary afferent pain fibers (nociceptors), but the extent to which functional TRPV1 channels are expressed in the central nervous system (CNS) is debated. As previous evidence is based largely on indirect physiological responses to capsaicin, here we genetically modified the TrpV1 locus to reveal, with excellent sensitivity and specificity, the distribution of TRPV1 in all neuronal and non-neuronal tissues. In contrast to reports of widespread and robust expression in the CNS, we find that neuronal TRPV1 is largely restricted to nociceptors in primary sensory ganglia, with minimal expression in a few discrete brain regions, most notably in a contiguous band of cells within and adjacent to the caudal hypothalamus. We confirm hypothalamic expression in the mouse using several complementary approaches, including in situ hybridization, calcium imaging, and electrophysiological recordings. Additional in situ hybridization experiments in rat, monkey and human brain demonstrate that the restricted expression of TRPV1 in the CNS is conserved across species. Outside of the CNS, we find TRPV1 expression in a subset of arteriolar smooth muscle cells within thermoregulatory tissues. Here, capsaicin increases calcium uptake and induces vasoconstriction, an effect that likely counteracts the vasodilation produced by activation of neuronal TRPV1.